Abstract

Background: So far, the neural network associated with posttraumatic stress disorder (PTSD) has been suggested to mainly involve the amygdala, hippocampus and medial prefrontal cortex. However, increasing evidence indicates that cortical regions extending beyond this network might also be implicated in the pathophysiology of PTSD. We aimed to investigate PTSD-related structural alterations in some of these regions.

Methods: We enrolled highly traumatized refugees with and without (traumatized controls) PTSD and nontraumatized controls in the study. To increase the validity of our results, we combined an automatic cortical parcellation technique and voxel-based morphometry.

Results: In all, 39 refugees (20 with and 19 without PTSD) and 13 controls participated in the study. Participants were middle-aged men who were free of psychoactive substances and consumed little to no alcohol. Patients with PTSD (and to a lesser extent traumatized controls) showed reduced volumes in the right inferior parietal cortex, the left rostral middle frontal cortex, the bilateral lateral orbitofrontal cortex and the bilateral isthmus of the cingulate. An influence of cumulative traumatic stress on the isthmus of the cingulate and the lateral orbitofrontal cortex indicated that, at least in these regions, structural alterations might be associated with repeated stress experiences. Voxel-based morphometry analyses produced largely consistent results, but because of a poorer signal-to-noise ratio, conventional statistics did not reach significance.

Limitations: Although we controlled for several important confounding variables (e.g., sex, alcohol abuse) with our particular sample, this might limit the generalizibility of our data. Moreover, high comorbidity of PTSD and major depression hinders a definite separation of these conditions in our findings. Finally, the results concerning the lateral orbito frontal cortex should be interpreted with caution, as magnetic resonance imaging acquisition in this region is affected by a general signal loss.

Conclusion: Our results indicate that lateral prefrontal, parietal and posterior midline structures are implicated in the pathophysiology of PTSD. As these regions are particularly involved in episodic memory, emotional processing and executive control, this might have important implications for the understanding of PTSD symptoms.

Competing interests: This research was supported by the German Research Foundation (DFG); the DFG had no further role in study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the paper for publication. None of the authors reported any biomedical financial interest or potential conflicts of interest.

Contributors: All authors contributed to study design and approved the article’s publication. Dr. Eckart recruited and assessed the participants. Drs. Eckart, Kaufmann and Tempelmann gathered MRI data. Drs. Eckart, Stoppel, Kaufmann and Tempelmann analyzed the data. Drs. Eckart and Stoppel wrote the initial draft of the manuscript, which was critically reviewed by Drs. Elbert and Kolassa. All authors discussed the results and implications and commented on the manuscript at all stages.